The long-term effects of in utero exposure to organochlorine compounds is of great potential importance. These compounds, which are detectable in nearly 100% of humans worldwide, have been linked to impaired neurodevelopment in children. In addition, p,p'-DDE, the primary metabolite of DDT, is a weak estrogen, and an androgen receptor blocker at concentrations observed in humans. One objective of this project is to determine whether maternal serum concentration of DDE, obtained during pregnancy, is a risk factor for cryptorchidism, hypospadias and polythelia in male offspring. These malformations were chosen because they are markers of deficient androgen activity in utero. Other objectives are to determine whether in utero exposure to DDE is subsequently associated with an altered age at menarche in adolescent females and an increased risk of obesity in adolescent males, and whether in utero exposure to PCBs is associated with suboptimal muscle tone, reflexes, IQ and hearing during childhood. Work to date has demonstrated that these compounds can be recovered from the study population at relevant concentrations, and that the correlation between concentrations of these compounds in first and third trimester serum is sufficiently high to employ third-trimester serum as a surrogate for first-trimester exposure. Work completed in FY 2002 found that elevated maternal serum DDE was associated with a history of fetal loss (odds ratio for 60 mg/l=1.3, p for trend <0.05). Since DDT is still used for malaria control in many developing countries, these findings have important implications for international health. It was also found that maternal third-trimester serum PCB levels were not associated with adverse neurodevelopment in children at 8 months of age, although substantial center heterogeneity was noted. Work completed in 2003 demonstrated that in contrast to animal toxicology study results, maternal PCB exposure was not associated with sensorineural hearing loss in the offspring, nor was PCB exposure associated with cognitive ability at age 7. Work is in progress in the study of maternal serum DDE and PCB concentration as risk factors for prolonged time to achieve pregnancy.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Pierik, Frank H; Klebanoff, Mark A; Brock, John W et al. (2007) Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring. Environ Res 105:364-9
Ribas-Fito, Nuria; Gladen, Beth C; Brock, John W et al. (2006) Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p'-DDE) in relation to child growth. Int J Epidemiol 35:853-8
Longnecker, Matthew P; Klebanoff, Mark A; Dunson, David B et al. (2005) Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies. Environ Res 97:127-33
Longnecker, Matthew P (2005) Invited Commentary: Why DDT matters now. Am J Epidemiol 162:726-8
Cooper, Glinda S; Klebanoff, Mark A; Promislow, Joanne et al. (2005) Polychlorinated biphenyls and menstrual cycle characteristics. Epidemiology 16:191-200
Law, Dionne C Gesink; Klebanoff, Mark A; Brock, John W et al. (2005) Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and time to pregnancy. Am J Epidemiol 162:523-32
Gray, Kimberly A; Klebanoff, Mark A; Brock, John W et al. (2005) In utero exposure to background levels of polychlorinated biphenyls and cognitive functioning among school-age children. Am J Epidemiol 162:17-26
Gladen, Beth C; Klebanoff, Mark A; Hediger, Mary L et al. (2004) Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males. Environ Health Perspect 112:1761-7
Longnecker, Matthew P; Hoffman, Howard J; Klebanoff, Mark A et al. (2004) In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children. Neurotoxicol Teratol 26:629-37
Daniels, Julie L; Longnecker, Matthew P; Klebanoff, Mark A et al. (2003) Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months. Am J Epidemiol 157:485-92

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